ERK1-mediated immunomodulation of mesenchymal stem cells ameliorates inflammatory disorders

Immune system disorders, especially T cell disorders, are important therapeutic targets of mesenchymal stem cells (MSCs) in many autoimmune diseases (ADs). Although extracellular regulated protein kinases (ERKs) play a role in MSC therapy by promoting T cell apoptosis, the mechanism remains unclear. Our findings indicate that ERK1(-/-) bone marrow MSCs (BMMSCs), but not ERK2(-/-) BMMSCs, failed to promote T cell apoptosis due to incapacity to activate the ETS2/AURKA/NF-kappa B/Fas/MCP-1 cascade. Moreover, ERK1(-/-) BMMSCs were unable to upregulate regulatory T cells and suppress T helper 17 cells. Licochalcone A (LA), which promotes ERK pathway activation, enhanced the therapeutic efficacy of MSC therapy in ulcerative colitis and collagen-induced arthritis mice. Our findings suggest that ERK1, but not ERK2, plays a crucial role in regulating T cells in MSCs. LA-treated MSCs provide a strategy to improve the efficacy of MSC-based treatments for ADs.

Automated summary

Immune system disorders, especially T cell disorders, are important therapeutic targets of mesenchymal stem cells (MSCs) in many autoimmune diseases (ADs). ERK1 plays a crucial role in regulating T cells in MSCs, and MSCs treated with LA can improve the efficacy of MSC-based treatments for ADs.